The unfolded protein response in relation to mitochondrial biogenesis in skeletal muscle cells.

THE UNFOLDED PROTEIN RESPONSE IN RELATION TO MITOCHONDRIAL BIOGENESIS IN SKELETAL MUSCLE CELLS.
Am J Physiol Cell Physiol. 2017 Mar 08;:ajpcell.00320.2016
Authors: Mesbah Moosavi ZS, Hood DA
Abstract
Mitochondria are comprised of both nuclear- and mitochondrially-encoded proteins requiring precise stoichiometry for their integration into functional complexes. The augmented protein synthesis associated with mitochondrial biogenesis results in the accumulation of unfolded proteins, thus triggering cellular stress. As such, the unfolded protein responses emanating from the endoplasmic reticulum (UPR(ER)) or the mitochondrion (UPR(MT)) are triggered to ensure correct protein handling. Whether this response is necessary for mitochondrial adaptations is unknown. Two models of mitochondrial biogenesis were used: muscle differentiation and chronic contractile activity (CCA) in murine muscle cells. After 4 days of differentiation, our findings depict selective activation of the UPR(MT) in which chaperones decreased, however Sirt3 and UPR(ER) markers were elevated. To delineate the role of ER stress in mitochondrial adaptations, the ER stress inhibitor TUDCA was administered. Surprisingly, mitochondrial markers COX-I, COX-IV, and PGC-1α protein levels were augmented up to 1.5-fold above that of vehicle-treated cells. Similar results were obtained in myotubes undergoing CCA in which biogenesis was enhanced by ~2-3-fold, along with elevated UPR...

Source: Am J Physiol Cell Ph... - March 7, 2017 Category: Cytology Authors: Mesbah Moosavi ZS, Hood DA Tags: Am J Physiol Cell Physiol Source Type: research